Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus (Madhumeha): A study protocol

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Insulin resistance leads to an increase in plasma fatty acids, which reduces transfer of glucose within the cells of muscles and increases breakage of lipids, resulting in an increase in hepatic glucose production. Nishamalaki (a formulation of turmeric and Indian gooseberry) is suggested in the therapy of all kinds of Madhumeha (diabetes mellitus) in Ayurveda classics. Turmeric and Indian gooseberry are the two main ingredients. Both are considered as effective medicines in the management of Madhumeha individually as well as in combined form. Aim To compare the efficacy of Nishaamalaki and metformin in obese patients of type2 diabetes mellitus. Methods The study will include 60 obese type 2 diabetes mellitus patients who will be distributed into two distinct categories, each with 30 patients. Nishamalaki Churna 3gm two times a day before food with warm water for 60 days in Group N (Experimental Group) and 500 mg metformin tablets twice daily before meals for 60 days in Group M (Control Group). Every 15th day, an assessment will be made (15th, 30th, 45th and 60th day). Results Objective outcomes will be assessed. Conclusion Conclusion will be based on the data received after the completion of the study. 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F1000Research 2024, 12 :1199 ( https://doi.org/10.12688/f1000research.139045.3 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Study Protocol Revised Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] Dr. Aman Chhabra https://orcid.org/0000-0001-8791-4902 1 , Vaishali Kuchewar 1 , Twinkle Joshi 1 Dr. Aman Chhabra https://orcid.org/0000-0001-8791-4902 1 , Vaishali Kuchewar 1 , Twinkle Joshi 1 PUBLISHED 04 Mar 2024 Author details Author details 1 Kayachikitsa, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India Dr. Aman Chhabra Roles: Investigation, Methodology, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Vaishali Kuchewar Roles: Conceptualization, Funding Acquisition, Methodology, Supervision, Validation, Writing – Review & Editing Twinkle Joshi Roles: Conceptualization, Supervision, Visualization OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Datta Meghe Institute of Higher Education and Research collection. Abstract Background Poor synthesis of insulin by beta cells present in the pancreas combined with resistance of insulin in peripheral organs is referred to as type 2 diabetes mellitus. Insulin resistance leads to an increase in plasma fatty acids, which reduces transfer of glucose within the cells of muscles and increases breakage of lipids, resulting in an increase in hepatic glucose production. Nishamalaki (a formulation of turmeric and Indian gooseberry) is suggested in the therapy of all kinds of Madhumeha (diabetes mellitus) in Ayurveda classics. Turmeric and Indian gooseberry are the two main ingredients. Both are considered as effective medicines in the management of Madhumeha individually as well as in combined form. Aim To compare the efficacy of Nishaamalaki and metformin in obese patients of type2 diabetes mellitus. Methods The study will include 60 obese type 2 diabetes mellitus patients who will be distributed into two distinct categories, each with 30 patients. Nishamalaki Churna 3gm two times a day before food with warm water for 60 days in Group N (Experimental Group) and 500 mg metformin tablets twice daily before meals for 60 days in Group M (Control Group). Every 15th day, an assessment will be made (15th, 30th, 45th and 60th day). Results Objective outcomes will be assessed. Conclusion Conclusion will be based on the data received after the completion of the study. READ ALL READ LESS Keywords Nishaamalaki Churna, Metformin, Obese Type2 Diabetes Mellitus Corresponding Author(s) Dr. Aman Chhabra ( [email protected] ) Close Corresponding author: Dr. Aman Chhabra Competing interests: No competing interests were disclosed. Grant information: This work is supported by an intramural grant from Datta Meghe Institute of Higher Education and Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2024 Chhabra DA et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Chhabra DA, Kuchewar V and Joshi T. Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.12688/f1000research.139045.3 ) First published: 25 Sep 2023, 12 :1199 ( https://doi.org/10.12688/f1000research.139045.1 ) Latest published: 04 Mar 2024, 12 :1199 ( https://doi.org/10.12688/f1000research.139045.3 ) Revised Amendments from Version 2 The tense used in the randomisation section is corrected now Study tool is used to denote Body mass Index instead of Investigations Durable efficacy is explained properly. The tense used in the randomisation section is corrected now Study tool is used to denote Body mass Index instead of Investigations Durable efficacy is explained properly. See the authors' detailed response to the review by Srihari Sheshagiri See the authors' detailed response to the review by Naushira Pandya See the authors' detailed response to the review by Supriya Bhalerao READ REVIEWER RESPONSES Introduction Poor pancreatic beta-cell insulin production accompanied by peripheral insulin resistance is referred to as type 2 diabetes mellitus. 1 Insulin resistance causes an increase in fatty acids in the plasma, resulting in reduced glucose transport into muscle cells and increased fat breakdown, which leads to an increase in hepatic glucose production. For type 2 diabetes mellitus to develop, insulin resistance and pancreatic-cell failure must both occur at the same time. Insulin resistance affects everyone who is overweight or obese, but diabetes only develops in those who don’t have enough insulin production to meet their level of insulin resistance. The prevalence of obesity has increased recently, highlighting the issue’s importance on a global scale. In the United States, almost two thirds of adults are thought to be overweight or obese. In many parts of the world, identical trends may be found. 2 Numerous physical, psychological, and social problems have been linked to obesity, the most significant of which is type 2 diabetes. 171 million individuals were predicted to have type 2 diabetes mellitus after the completion of this era, and by 2030, this figure is projected to reach 360 million. 3 The basic metabolism defect in type II Diabetes mellitus is either delayed insulin secretion relative to glucose load (impaired insulin secretion) or the peripheral tissue are unable to respond to insulin (insulin resistance) Type II Diabetes mellitus is a heterogeneous disorder with a more complex etiology and is far more common than type I, but much less is known about its pathogenesis. The drug metformin is now routinely used to treat diabetes mellitus. With lifestyle changes, it is now regarded as the first line of treatment for type 2 diabetes mellitus because of its outstanding safety standards, effectiveness, tolerability, and high hypoglycaemia. 4 Excitingly, epidemiological, and preclinical studies have recently shown that metformin has positive effects in addition to its effects on Glycaemic indices. It has been demonstrated to lower body weight, reduce cancer incidence and death, and extend longevity. 4 Metformin has been a popular study topic for disorders related to obesity and ageing as a result of these effects. Nishaamalaki is suggested in the management of obese patients suffering from diabetes mellitus in Ayurveda classics. 5 Turmeric and Indian gooseberry are the two main ingredients. Both are individually as well as in combined form are considered as effective medicines in the management of Madhumeha (diabetes mellitus). In experimental animal models, its rhizomes were shown to exhibit anti-diabetic characteristics. Curcumin, the key component, was shown to have anti-diabetic properties, according to researchers. 6 In one animal study, it is also found to be a weight reducing agent. 7 Indian gooseberry contains Ellagic acid which exhibits blood sugar lowering effects by stimulating insulin production and decreasing glucose intolerance in diabetic rats. Immunohistochemistry of the pancreas revealed that in diabetic rats, Indian gooseberry increased Beta cell size as well as its count. Additionally, it decreased the glucose intolerance of diabetic rats and raised the generation of insulin stimulated by blood glucose from isolated islets. 8 Some of the main compounds in the fruits of Emblica officinalis (such as gallotanin, corilagin, and ellagic acid) have blood glucose lowering qualities due to their characteristics of free radical scavenging, according to studies. Hyperglycaemia, heart problems, diabetic nephropathy, neuropathy, cataractogenesis, and other conditions have all been linked to it. 9 Amalaki is rich in vitamin C. It has been shown that taking extra vitamin C helps diabetics with sorbitol build-up in their red blood cells. Vitamin C also lessens capillary fragility, which increases the risk of complications from diabetes. 10 Additionally, previous research indicates that prolonged vitamin C treatment has advantageous effects on lipid and glucose metabolism in T2DM patients. 11 Type 2 diabetes mellitus and obesity are progressive and rapidly spreading metabolic diseases. Both have strong correlation. In modern medicine, it is studied that metformin has antidiabetic as well as anti-obesity effect. There are numerous studies on Nisha-amalaki showing its antidiabetic effect, but it is not studied in obese type 2 diabetic patients hence this study is planned. Methods Study design This single-blind, randomised, standard-controlled experiment includes a parallel group. A 60-day treatment term and a 15-day follow-up period are both included in the trial. A total of 60 patients are chosen for the trial, and they will be distributed into 2 equal groups according to the allocation ratio. Group M is a conventional standard group while Group N is a trial group. Study setting Recruitment of patients will take place at MGACH&RC, Wardha, from the OPD and IPD of the Department of Kayachikitsa. Patients will also be chosen from a variety of peripheral camps with diverse specialties. Trial registration number : This trial has the CTRI registration number CTRI/2021/10/037263. Diagnostic criteria: The patients will be assessed based on blood sugar level (Fasting and Postprandial) and Body Mass Index. Eligibility criteria: Age between 30 to 60 years of either sex. Patients having Fasting Blood Sugar Level >126 mg/dL and/or Postprandial Blood Sugar Level >200 mg/dL. B.M.I. in between 25-30 kg/m 2 . Interventions Group N – Nishamalaki Churna 3 gm two times a day before meals. Group M – 500 mg metformin tablets two times a day before meals. Randomization Participants will meet the criteria for randomization, and they will be assigned to the experimental and control groups in a 1:1 ratio. A lottery-based randomization system that operates remotely provided researchers with access to the treatment allocation for each eligible participant. A total of 60 patients will be chosen for the trial, and they will be distributed into 2 equal groups. The experimental group is Group N, while the usual controlled group is Group M. Folded slips of both metformin as well as Nishaamalaki will be kept in a bowl and patients will be asked to choose any one of the slips. After which the patient will be allocated to that particular group which he/she will choose. Blinding treatment The assignments will be kept a secret until the trial is finished. The will all be blinded. Throughout the trial, doctors evaluate all of the participants. Using the lottery-based method of randomization of patients, the practitioner applied for a randomised assignment for each eligible patient, and a prescription for “ Nishamalaki Churna with honey before meal two times a day” was written. The patients will then be escorted to the Dattatraya Rasa Shala’s designated drug managers, accompanied by a study assistant. All of the medications are packed in the same way. The actual names of both the groups, i.e. , standard as well as trial groups will be kept blinded unless any adverse event or side effect of any of the group is observed. Screening investigations (base line): Fasting Blood Sugar, Postprandial Blood Sugar. Study tools used: Body Mass Index. Investigation (end line): Fasting Blood Sugar, Postprandial Blood Sugar. Withdrawal criteria • Subjects will be withdrawn from the trial if any unintended occurrence, signs of reaction of medication, adverse or side effect emerged, and the therapy will be supplied to such a patient totally free of cost until the difficulty subsided. We will measure the amount of Churna consumed to assess and monitor drug adherence, and the subject will be monitored during therapy. Follow-up Follow up of patients will be done in every 15 days during treatment. Results • Primary: Clinicians will examine the impact of therapeutic drugs on blood sugar levels (Fasting and Post meal). • Secondary: To study the reduction of B.M.I. Score. • Durable efficacy: Respondents will be categorised as durable efficacy responders if they get desirable improvement for a minimum of one month during treatment. If the patients got decreased level of Fasting blood sugar level, Postprandial blood sugar level and/or Body Mass Index, then the results will be considered as durable efficacious. Analytical statistics A level of significance of 5% (two-sided) will be regarded statistically significant. Intention-to-treat and in accordance with protocol populations will be used in the analysis. For each group, baseline characteristics will be offered, as well as predicting factors. We shall express discrete variables with percentages and frequencies from baseline to each time point, whereas for data with a distribution that is normal, variables that are continuous can be characterised by the mean or standard deviation, or by the median and interquartile range, for data with an irregular distribution. Paired and unpaired t tests will be performed to assess the Results for each time point’s comparisons between the trial and standard groups. Predictive factor analysis will be performed with the following two steps: The univariate analysis is the initial phase. The sufficient alleviation follow-up responder rates (day 15 and 30) will be employed as dependent variables, with predictor variables such as demographic and clinical features, as well as important elements of Nishamalaki Churna , serving as independent variables. An analysis of logistic regression will be carried out. The independent variable’s selection criteria are defined as = 0.1. Multivariate analysis is the next phase. The predicted factors chosen in initial phase will be incorporated into 2 different models of regression with the desirable improvement pattern of the patient as the variable which is dependent on the other one (day 45). It was decided to do a sensitivity analysis. The main and safety outcomes will be compared across all randomised respondents. Recruitment: The patients will be enrolled and assigned by the principal investigator. Methods: Data collection, analysis, and management. Objectives: BS-PP, FBS (at the start and end of the treatment). The assessment will be done using the values at the start of the study, and on the 60th day (after treatment). The therapeutic strategy will be overseen by the main examiner, who contacted the respondents and kept track of their progress in paperwork. Plan to ensure that participants are retained, and that all follow-up is completed: By getting the patient’s phone number, we may stay in touch while giving them timely medication and advice for the follow-up, with the information from the follow-up being justifiably stored in the paperwork. Management of data Patients’ data will be gathered through clinical examination. The main examiner will enter the data into the master sheet, assess it using the appropriate statistical method, and code the data. Consent Before the trial begins, patients will be asked for their written informed permission. Ethical approval The study was approved by the Institutional Ethics Committee, letterno. MGACHRC/IEC/July/2021/331. Results The methods may work to lower blood sugar levels (fasting and post-meal) in the trial and control group. Implementing suitable dietary regimen and proper exercise during treatment may decrease the likelihood of return of symptoms compared to taking regular metformin tablets for the patient. Discussion This study will compare the therapeutic efficacy of Nishamalaki Churna with honey and metformin tablets in individuals with type 2 diabetes mellitus who are obese. Nishamalaki is mentioned as the effective management of Madhumeha (Type-2 DM) in Ayurveda classics, according to ayurvedic literature. Haridra ( Curcuma longa L ) is a preferred medicine for type 2 diabetes mellitus. Both Nishamalaki Churna with honey and metformin tablets were found to effectively lower FBS and BS-PP levels. Turmeric and Indian gooseberry are found in Nishamalaki Churna. Haridra (turmeric) in Veerya (potency) is Ushna (hot) , and Tikta Rasa (bitter) is useful in Kaphaja Vikaras (disorders related to kapha biohumour). These substances contain qualities such as Ruksha (dry) , Ushna (hot) , Tishna (bitter), and Katu Vipaka (pungent), which aid in Samprapti Vighatana (pathogenesis) and hence aid in managing the obese patients suffering from Type-2 DM. However, in this work, we will look at the differences in both formulations and their influence on objective metrics. In obese type 2 diabetes mellitus, the total effects will reveal which formulation is effective. Conclusions Conclusion will be based on the data received after the completion of the study. Data availability No data is associated with this article. References 1. Kasuga M: Insulin resistance and pancreatic β cell failure. J. Clin. Investig. 2006; 116 (7): 1756–1760. PubMed Abstract | Publisher Full Text | Free Full Text 2. Tsai AG, Williamson DF, Glick HA: Direct medical cost of overweight and obesity in the USA: a quantitative systematic review. Obes. Rev. 2011; 12 (1): 50–61. PubMed Abstract | Publisher Full Text | Free Full Text 3. McKeigue PM, Shah B, Marmot MG: Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet. 1991; 337 (8738): 382–386. PubMed Abstract | Publisher Full Text 4. American Diabetes, A: Standards of Medical Care in Diabetes-2019 Abridged for Primary Care Providers. Clin. Diabetes. 2019; 37 (1): 11–34. PubMed Abstract | Publisher Full Text | Free Full Text 5. Agnivesha C: Charaka Samhita reprint: 2011, edited by Vaidya Yadavaji Trikamji Acharya, Chaukhamba Surbharati Prakashana, Varanasi. Chikitsasthana Prameha Chikitsa Adhyaya 6/26;447. 6. Perera PK, Li Y: Functional herbal food ingredients used in type 2 Diabetes Mellitus. Pharm. Rev. 2012; 6 (11): 37–45. Jan-Jun. Publisher Full Text 7. Dawane JS, Pandit V: Study the efficacy of herbal formulation Niśha-āmalakī in animal model of polycystic ovarian disease syndrome. ASL. 2019; 37 (2): 86–93. 8. Fatima N, Hafizur RM, Hameed A, et al. : NurulKabir, Ellagic acid in Emblicaofficinalis exerts anti-diabetic activity through the action on β-cells of pancreas. Eur. J. Nutr. 2017 Mar; 56 (2): 591–601. PubMed Abstract | Publisher Full Text 9. D’Souza JJ, D’Souza PP, Fazal F, et al. : Anti-diabetic effects of the Indian indigenous fruit EmblicaofficinalisGaertn : active constituents and modes of action. FoodFunct. 2014 Apr; 5 (4): 635–644. Publisher Full Text 10. Cunningham JJ, Mearkle PL, Brown RG: Vitamin C: an aldose reductase inhibitor that normalizes erythrocyte sorbitol in insulin-dependent Diabetes Mellitus. J. Am. Coll. Nutr. 1994; 13 : 344–350. PubMed Abstract | Publisher Full Text 11. Srivasuki KP: Nutritional and health care benefits of Amla. J. Pharmacogn. 2012; 3 (2): 141–151. Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 25 Sep 2023 ADD YOUR COMMENT Comment Author details Author details 1 Kayachikitsa, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India Dr. Aman Chhabra Roles: Investigation, Methodology, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Vaishali Kuchewar Roles: Conceptualization, Funding Acquisition, Methodology, Supervision, Validation, Writing – Review & Editing Twinkle Joshi Roles: Conceptualization, Supervision, Visualization Competing interests No competing interests were disclosed. Grant information This work is supported by an intramural grant from Datta Meghe Institute of Higher Education and Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (3) version 3 Revised Published: 04 Mar 2024, 12:1199 https://doi.org/10.12688/f1000research.139045.3 version 2 Revised Published: 24 Nov 2023, 12:1199 https://doi.org/10.12688/f1000research.139045.2 version 1 Published: 25 Sep 2023, 12:1199 https://doi.org/10.12688/f1000research.139045.1 Copyright © 2024 Chhabra DA et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Chhabra DA, Kuchewar V and Joshi T. Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.12688/f1000research.139045.3 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 3 VERSION 3 PUBLISHED 04 Mar 2024 Revised Views 0 Cite How to cite this report: Tjandrawinata R. Reviewer Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.163086.r353713 ) The direct URL for this report is: https://f1000research.com/articles/12-1199/v3#referee-response-353713 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 07 Jan 2025 Raymond Tjandrawinata , Atma Jaya Catholic University of Indonesia, South Jakarta, Indonesia Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.163086.r353713 The protocol compares Nishaamalaki Churna with metformin for treating obese patients with type 2 diabetes mellitus (T2DM). The rationale is partly clear, as the study objective shifts focus between glycemic control and obesity without clearly differentiating the primary aim. The randomized design ... Continue reading READ ALL The protocol compares Nishaamalaki Churna with metformin for treating obese patients with type 2 diabetes mellitus (T2DM). The rationale is partly clear, as the study objective shifts focus between glycemic control and obesity without clearly differentiating the primary aim. The randomized design is appropriate, but blinding is problematic due to the differing forms of the drugs. Methodological details are insufficient, lacking clarity on sample size calculation, randomization, and adherence tracking. BMI is misclassified as an investigation instead of a study tool. Secondary outcomes could be expanded to better reflect obesity management. Ethical considerations and data-sharing plans need elaboration. Grammatical inconsistencies and premature conclusions predicting results need correction. Key Points for Scientific Soundness: Clarify the primary objective – whether the focus is glycemic control, obesity, or both. Address the limitations of blinding and correct BMI classification as a study tool. Provide comprehensive methodological details on sample size, randomization, and compliance monitoring. Expand secondary outcomes and specify ethical considerations and data-sharing practices. Addressing these issues will enhance the protocol’s clarity and reproducibility, improving its scientific rigor. Is the rationale for, and objectives of, the study clearly described? Partly Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? No Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Pharmacology and Molecular Medicine I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Tjandrawinata R. Reviewer Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.163086.r353713 ) The direct URL for this report is: https://f1000research.com/articles/12-1199/v3#referee-response-353713 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Hashimoto Y. Reviewer Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.163086.r286660 ) The direct URL for this report is: https://f1000research.com/articles/12-1199/v3#referee-response-286660 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 10 Jun 2024 Yoshitaka Hashimoto , Matsushita Memorial Hospital, Moriguchi, Japan Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.163086.r286660 This protocol study will examine the effect of Nishaamalaki i n obese patients with type 2 diabetes mellitus. Several problems should be resolved. 1. Sample size. How to calculate the sample size was unclear. 2. Inclusion criteria were ... Continue reading READ ALL This protocol study will examine the effect of Nishaamalaki i n obese patients with type 2 diabetes mellitus. Several problems should be resolved. 1. Sample size. How to calculate the sample size was unclear. 2. Inclusion criteria were also unclear. The patients who were already used the medications for diabetes (without metformin) can participate? 3. BS-PP, FBS: These words should be spelled out. Furthermore, are FBS and BS-PP measured on the same day? How many minutes after a meal is BS-PP? Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? No Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Diabetes, obesity I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Hashimoto Y. Reviewer Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.163086.r286660 ) The direct URL for this report is: https://f1000research.com/articles/12-1199/v3#referee-response-286660 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 2 VERSION 2 PUBLISHED 24 Nov 2023 Revised Views 0 Cite How to cite this report: Sheshagiri S. Reviewer Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.159185.r225291 ) The direct URL for this report is: https://f1000research.com/articles/12-1199/v2#referee-response-225291 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 08 Feb 2024 Srihari Sheshagiri , Department of PG Studies in Kaumarabhritya, JSS Ayurvedic Medical College, Mysore, Karnataka, India Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.159185.r225291 1. Blinding may not be appropriate as two different forms of medicines are being administered. 2. Words used in the Randomisation paragraph (in methods section) are in past tense implying that the study is already concluded. The ... Continue reading READ ALL 1. Blinding may not be appropriate as two different forms of medicines are being administered. 2. Words used in the Randomisation paragraph (in methods section) are in past tense implying that the study is already concluded. The same needs proper grammatical correction. 3. What is the 'durable efficacy' in results needs to be defined 4. BMI is not an investigation rather an examination tool. The same can be removed from screening investigations, or the term tools can be used instead of investigation Competing Interests: No competing interests were disclosed. Reviewer Expertise: Ayurveda, Pediatrics I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Sheshagiri S. Reviewer Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.159185.r225291 ) The direct URL for this report is: https://f1000research.com/articles/12-1199/v2#referee-response-225291 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 13 Apr 2024 Dr. Aman Chhabra , Kayachikitsa, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India 13 Apr 2024 Author Response Respected Sir Thanks for the comments given by you on my protocol. I would like to respond you with the rectifications in the comments. 1. The medicines in both the ... Continue reading Respected Sir Thanks for the comments given by you on my protocol. I would like to respond you with the rectifications in the comments. 1. The medicines in both the groups will be given separately to each patient with a proper randomisation. That's why the blinding is kept as appropriate even being two different forms of medicines. 2. The tense for the words used in Randimisation paragraph are now rectified. 3. Durable efficacy in results is now defined. 4. The term tools will be used instead of investigation as per your suggestion. Respected Sir Thanks for the comments given by you on my protocol. I would like to respond you with the rectifications in the comments. 1. The medicines in both the groups will be given separately to each patient with a proper randomisation. That's why the blinding is kept as appropriate even being two different forms of medicines. 2. The tense for the words used in Randimisation paragraph are now rectified. 3. Durable efficacy in results is now defined. 4. The term tools will be used instead of investigation as per your suggestion. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 13 Apr 2024 Dr. Aman Chhabra , Kayachikitsa, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India 13 Apr 2024 Author Response Respected Sir Thanks for the comments given by you on my protocol. I would like to respond you with the rectifications in the comments. 1. The medicines in both the ... Continue reading Respected Sir Thanks for the comments given by you on my protocol. I would like to respond you with the rectifications in the comments. 1. The medicines in both the groups will be given separately to each patient with a proper randomisation. That's why the blinding is kept as appropriate even being two different forms of medicines. 2. The tense for the words used in Randimisation paragraph are now rectified. 3. Durable efficacy in results is now defined. 4. The term tools will be used instead of investigation as per your suggestion. Respected Sir Thanks for the comments given by you on my protocol. I would like to respond you with the rectifications in the comments. 1. The medicines in both the groups will be given separately to each patient with a proper randomisation. That's why the blinding is kept as appropriate even being two different forms of medicines. 2. The tense for the words used in Randimisation paragraph are now rectified. 3. Durable efficacy in results is now defined. 4. The term tools will be used instead of investigation as per your suggestion. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 25 Sep 2023 Views 0 Cite How to cite this report: Sheshagiri S. Reviewer Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.152287.r210017 ) The direct URL for this report is: https://f1000research.com/articles/12-1199/v1#referee-response-210017 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 21 Nov 2023 Srihari Sheshagiri , Department of PG Studies in Kaumarabhritya, JSS Ayurvedic Medical College, Mysore, Karnataka, India Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.152287.r210017 Grammatical errors needs corrections, in few area present tense and in few area past tense has been utilised by the authors. In methods (abstract), inclusion of obese type 2 patients have been ... Continue reading READ ALL Grammatical errors needs corrections, in few area present tense and in few area past tense has been utilised by the authors. In methods (abstract), inclusion of obese type 2 patients have been said a criteria for inclusion however in the article, BMI of 25-30 has been mentioned. One of the criteria to call a person obese is BMI above 30. Hence this needs clarity. Comparing the efficacy of trial drug and standard group has been mentioned as secondary outcome. However, the same a been mentioned as the main aim in abstract and in conclusion of the article. The same needs clarification. Is the rationale for, and objectives of, the study clearly described? Partly Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Partly Are the datasets clearly presented in a useable and accessible format? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Ayurveda, Pediatrics I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Sheshagiri S. Reviewer Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.152287.r210017 ) The direct URL for this report is: https://f1000research.com/articles/12-1199/v1#referee-response-210017 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 30 Nov 2023 Dr. Aman Chhabra , Kayavhikitsa, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India 30 Nov 2023 Author Response Respected Sir, Thanks for your valuable review and comments on my manuscript. I would like to respond and clarify the comments given one by one. 1. Grammatical errors are ... Continue reading Respected Sir, Thanks for your valuable review and comments on my manuscript. I would like to respond and clarify the comments given one by one. 1. Grammatical errors are now corrected and the entire manuscript is framed in future tense as per the guidelines for a protocol. 2. As per W.H.O., Obesity is a general term in which criteria of overweight has a classification of having B.M.I. score of 25-30 kg/m 2 , which is actually taken into consideration for this study protocol. , 3. The secondary outcome is now updated for better clarification. I request you to kindly review the corrected manuscript and if you feel satisfied with the corrections, kindly give your approval so as to proceed further in the peer review process. Looking forward for your kind response. Thanks Respected Sir, Thanks for your valuable review and comments on my manuscript. I would like to respond and clarify the comments given one by one. 1. Grammatical errors are now corrected and the entire manuscript is framed in future tense as per the guidelines for a protocol. 2. As per W.H.O., Obesity is a general term in which criteria of overweight has a classification of having B.M.I. score of 25-30 kg/m 2 , which is actually taken into consideration for this study protocol. , 3. The secondary outcome is now updated for better clarification. I request you to kindly review the corrected manuscript and if you feel satisfied with the corrections, kindly give your approval so as to proceed further in the peer review process. Looking forward for your kind response. Thanks Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 30 Nov 2023 Dr. Aman Chhabra , Kayavhikitsa, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India 30 Nov 2023 Author Response Respected Sir, Thanks for your valuable review and comments on my manuscript. I would like to respond and clarify the comments given one by one. 1. Grammatical errors are ... Continue reading Respected Sir, Thanks for your valuable review and comments on my manuscript. I would like to respond and clarify the comments given one by one. 1. Grammatical errors are now corrected and the entire manuscript is framed in future tense as per the guidelines for a protocol. 2. As per W.H.O., Obesity is a general term in which criteria of overweight has a classification of having B.M.I. score of 25-30 kg/m 2 , which is actually taken into consideration for this study protocol. , 3. The secondary outcome is now updated for better clarification. I request you to kindly review the corrected manuscript and if you feel satisfied with the corrections, kindly give your approval so as to proceed further in the peer review process. Looking forward for your kind response. Thanks Respected Sir, Thanks for your valuable review and comments on my manuscript. I would like to respond and clarify the comments given one by one. 1. Grammatical errors are now corrected and the entire manuscript is framed in future tense as per the guidelines for a protocol. 2. As per W.H.O., Obesity is a general term in which criteria of overweight has a classification of having B.M.I. score of 25-30 kg/m 2 , which is actually taken into consideration for this study protocol. , 3. The secondary outcome is now updated for better clarification. I request you to kindly review the corrected manuscript and if you feel satisfied with the corrections, kindly give your approval so as to proceed further in the peer review process. Looking forward for your kind response. Thanks Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Bhalerao S. Reviewer Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.152287.r213873 ) The direct URL for this report is: https://f1000research.com/articles/12-1199/v1#referee-response-213873 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 21 Nov 2023 Supriya Bhalerao , Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be) University, Pune, Maharashtra, India Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.152287.r213873 The protocol is for assessing the efficacy of Nishamalaki in obesity, then why the introduction refers more to diabetes? ‘Type of trial’ is wrong term. It should be ‘study design’. ... Continue reading READ ALL The protocol is for assessing the efficacy of Nishamalaki in obesity, then why the introduction refers more to diabetes? ‘Type of trial’ is wrong term. It should be ‘study design’. How the blinding is possible? The nature of study drug and control drug is completely different-it should be an open study. There are no variables reflecting improvement in obesity e.g. body composition or circumferences, lipid profile. How the FBS and PPBS can give idea about anti-obesity efficacy? The authors need to decide whether they wish to demonstrate the efficacy of study drug in obesity or in diabetes. Is the rationale for, and objectives of, the study clearly described? No Is the study design appropriate for the research question? No Are sufficient details of the methods provided to allow replication by others? No Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Obesity, Type 2 Diabetes, NAFLD, PCOS I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Bhalerao S. Reviewer Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.152287.r213873 ) The direct URL for this report is: https://f1000research.com/articles/12-1199/v1#referee-response-213873 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 30 Nov 2023 Dr. Aman Chhabra , Kayavhikitsa, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India 30 Nov 2023 Author Response Respected Mam, Thanks for your valuable review and comments on my manuscript. I would like to respond and clarify the comments one by one. 1. As mentioned in the ... Continue reading Respected Mam, Thanks for your valuable review and comments on my manuscript. I would like to respond and clarify the comments one by one. 1. As mentioned in the title, the study protocol is for assessing the efficacy of Nishaaamalaki and Metformin in obese patients suffering from Type-2 Diabetes Mellitus. The main focus is on Type-2 Diabetes Mellitus and not on obesity. Therefore, the Introduction refers more to Type-2 Diabetes Mellitus. 2. Type of trial is now replaced by Study design. 3. Blinding is for the allocation of groups not for the medicine. 4. Reduction in Body mass Index reflects improvement in obesity which is considered as the secondary outcome in this study. 5. It is totally clear and decided that the protocol is framed to compare the efficacy of trial and standard drug in obese patients suffering from Type-2 Diabetes Mellitus. I request you to kindly consider the responses and if you feel satisfied, then kindly give your necessary approval so that the peer review process can proceed further. Looking forward for your kind response. Thanks and Regards. Respected Mam, Thanks for your valuable review and comments on my manuscript. I would like to respond and clarify the comments one by one. 1. As mentioned in the title, the study protocol is for assessing the efficacy of Nishaaamalaki and Metformin in obese patients suffering from Type-2 Diabetes Mellitus. The main focus is on Type-2 Diabetes Mellitus and not on obesity. Therefore, the Introduction refers more to Type-2 Diabetes Mellitus. 2. Type of trial is now replaced by Study design. 3. Blinding is for the allocation of groups not for the medicine. 4. Reduction in Body mass Index reflects improvement in obesity which is considered as the secondary outcome in this study. 5. It is totally clear and decided that the protocol is framed to compare the efficacy of trial and standard drug in obese patients suffering from Type-2 Diabetes Mellitus. I request you to kindly consider the responses and if you feel satisfied, then kindly give your necessary approval so that the peer review process can proceed further. Looking forward for your kind response. Thanks and Regards. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 30 Nov 2023 Dr. Aman Chhabra , Kayavhikitsa, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India 30 Nov 2023 Author Response Respected Mam, Thanks for your valuable review and comments on my manuscript. I would like to respond and clarify the comments one by one. 1. As mentioned in the ... Continue reading Respected Mam, Thanks for your valuable review and comments on my manuscript. I would like to respond and clarify the comments one by one. 1. As mentioned in the title, the study protocol is for assessing the efficacy of Nishaaamalaki and Metformin in obese patients suffering from Type-2 Diabetes Mellitus. The main focus is on Type-2 Diabetes Mellitus and not on obesity. Therefore, the Introduction refers more to Type-2 Diabetes Mellitus. 2. Type of trial is now replaced by Study design. 3. Blinding is for the allocation of groups not for the medicine. 4. Reduction in Body mass Index reflects improvement in obesity which is considered as the secondary outcome in this study. 5. It is totally clear and decided that the protocol is framed to compare the efficacy of trial and standard drug in obese patients suffering from Type-2 Diabetes Mellitus. I request you to kindly consider the responses and if you feel satisfied, then kindly give your necessary approval so that the peer review process can proceed further. Looking forward for your kind response. Thanks and Regards. Respected Mam, Thanks for your valuable review and comments on my manuscript. I would like to respond and clarify the comments one by one. 1. As mentioned in the title, the study protocol is for assessing the efficacy of Nishaaamalaki and Metformin in obese patients suffering from Type-2 Diabetes Mellitus. The main focus is on Type-2 Diabetes Mellitus and not on obesity. Therefore, the Introduction refers more to Type-2 Diabetes Mellitus. 2. Type of trial is now replaced by Study design. 3. Blinding is for the allocation of groups not for the medicine. 4. Reduction in Body mass Index reflects improvement in obesity which is considered as the secondary outcome in this study. 5. It is totally clear and decided that the protocol is framed to compare the efficacy of trial and standard drug in obese patients suffering from Type-2 Diabetes Mellitus. I request you to kindly consider the responses and if you feel satisfied, then kindly give your necessary approval so that the peer review process can proceed further. Looking forward for your kind response. Thanks and Regards. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Pandya N. Reviewer Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.152287.r213867 ) The direct URL for this report is: https://f1000research.com/articles/12-1199/v1#referee-response-213867 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 16 Nov 2023 Naushira Pandya , Kiran Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.152287.r213867 Comments: 1.The mechanisms for T2 diabetes could be expanded (eg; hepatic glucose production, renal reabsorption etc). What is meant by completion of this era in paragraph 2 of the Introduction? 2. How was the ... Continue reading READ ALL Comments: 1.The mechanisms for T2 diabetes could be expanded (eg; hepatic glucose production, renal reabsorption etc). What is meant by completion of this era in paragraph 2 of the Introduction? 2. How was the number of study subjects decided? 3. Are the subjects also on other treatments for diabetes, or even metformin at higher doses? 4. Will there be assessment of glycemic control in subjects prior to intervention with A1C levels? 5. The term "diabetics" is no longer used due to patients' objections. They are people with diabetes, and not defined by diabetes. 6. How is the dosage of Nishamalaki standardized? Will the honey cause a rise in blood glucose? If drugs are packaged in the same way, will metformin also be dosed the same way? 7. Will subjects who may withdraw still be counted in the final results (intention to treat)? Removing their data will bias the results. 8. How often will fasting and postprandial BG be checked? The Analytics section mentions day 15, 30, 45 but the Objectives state measurements at the start and day 60. 9. Secondary outcomes is poorly formulated. Subjects already have the disease, so disease recurrence does not seem valid and is repeated in the text. Monitoring for adverse effects is standard and is not a secondary outcome. Unless specific outcomes such as hospitalization, hypoglycemia, weight loss are being studied. 10. Randomization through lottery method needs to be explained further. If randomized, they cannot be assigned to a control or treatment group. 11. Since this is a methods paper, the Results section cannot possibly predict the results. The same applies to the Discussion section which mentions both metformin and Nishamalaki were effective in lowering blood glucose levels without any data to prove this. 12. Other agents in food or spices that are thought to lower blood glucose may be in the introduction to provide context, but NOT in the Discussion of the paper which is based on a specific research question. 13. Similarly the Conclusion section is premature without data or proof. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? No Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Diabetes management in older adults I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Pandya N. Reviewer Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.152287.r213867 ) The direct URL for this report is: https://f1000research.com/articles/12-1199/v1#referee-response-213867 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 30 Nov 2023 Dr. Aman Chhabra , Kayavhikitsa, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India 30 Nov 2023 Author Response Respected Mam, Thanks for your valuable review and comments on my manuscript. I would like to respond on each comments given by you and do the necessary corrections in the ... Continue reading Respected Mam, Thanks for your valuable review and comments on my manuscript. I would like to respond on each comments given by you and do the necessary corrections in the study protocol as asked. I request you to kindly review the responses and corrections and give the approval if you find it appropriate as early as possible. 1. The mechanisms of T2 Diabetes mellitus will be explained in detail in the Introduction part. In paragraph 2 of the introduction part, by the end of this era means with the start of next generation. 2. The number of subjects are decided as per the appropriate statistical formula for calculating the sample size. 3. Subjects are not on any other treatment or any higher doses of metformin. They are asked to participate after the completion of a washout period of other previous medicines if any. 4. Assessment of glycemic control with HbA1C levels prior to intervention will not be done due to non-affordability of the patients to perform HBA1C test. 5. The term "diabetics" will be removed from the manuscript and will be replaced by "the patients suffering from Diabetes". 6. The dosage of Nishaamalaki is standardized by the dosage mentioned in classical texts of Ayurveda. Honey will not cause any rise in blood glucose level. A supporting mother article for this fact is available. Metformin and Nishamalaki, both are packaged and dosed in the same way. 7. Subjects who may withdraw the study will not be counted but will get replaced by other subjects until the calculated sample size gets completed. Therefore, it will not cause any bias. 8. Fasting and postprandial Blood glucose levels will be checked on day 0 and at day 60 as mentioned in the assessment criteria. 9. Secondary outcome will be properly formulated by mentioning the study of lowering BMI score. 10. Randomization through lottery method will be explained properly. 11. Result and discussion are just an expectation of the outcome, which will be completely based on the data received after the completion of study. 12. Other agents like food or spics that helps in the management of Diabetes Mellitus will be mentioned in the Introduction section instead of Discussion. 13. Conclusion will be formed only after receiving the data after completion of the study. Currently, it is merely an expectation. Respected Mam, Thanks for your valuable review and comments on my manuscript. I would like to respond on each comments given by you and do the necessary corrections in the study protocol as asked. I request you to kindly review the responses and corrections and give the approval if you find it appropriate as early as possible. 1. The mechanisms of T2 Diabetes mellitus will be explained in detail in the Introduction part. In paragraph 2 of the introduction part, by the end of this era means with the start of next generation. 2. The number of subjects are decided as per the appropriate statistical formula for calculating the sample size. 3. Subjects are not on any other treatment or any higher doses of metformin. They are asked to participate after the completion of a washout period of other previous medicines if any. 4. Assessment of glycemic control with HbA1C levels prior to intervention will not be done due to non-affordability of the patients to perform HBA1C test. 5. The term "diabetics" will be removed from the manuscript and will be replaced by "the patients suffering from Diabetes". 6. The dosage of Nishaamalaki is standardized by the dosage mentioned in classical texts of Ayurveda. Honey will not cause any rise in blood glucose level. A supporting mother article for this fact is available. Metformin and Nishamalaki, both are packaged and dosed in the same way. 7. Subjects who may withdraw the study will not be counted but will get replaced by other subjects until the calculated sample size gets completed. Therefore, it will not cause any bias. 8. Fasting and postprandial Blood glucose levels will be checked on day 0 and at day 60 as mentioned in the assessment criteria. 9. Secondary outcome will be properly formulated by mentioning the study of lowering BMI score. 10. Randomization through lottery method will be explained properly. 11. Result and discussion are just an expectation of the outcome, which will be completely based on the data received after the completion of study. 12. Other agents like food or spics that helps in the management of Diabetes Mellitus will be mentioned in the Introduction section instead of Discussion. 13. Conclusion will be formed only after receiving the data after completion of the study. Currently, it is merely an expectation. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 30 Nov 2023 Dr. Aman Chhabra , Kayavhikitsa, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India 30 Nov 2023 Author Response Respected Mam, Thanks for your valuable review and comments on my manuscript. I would like to respond on each comments given by you and do the necessary corrections in the ... Continue reading Respected Mam, Thanks for your valuable review and comments on my manuscript. I would like to respond on each comments given by you and do the necessary corrections in the study protocol as asked. I request you to kindly review the responses and corrections and give the approval if you find it appropriate as early as possible. 1. The mechanisms of T2 Diabetes mellitus will be explained in detail in the Introduction part. In paragraph 2 of the introduction part, by the end of this era means with the start of next generation. 2. The number of subjects are decided as per the appropriate statistical formula for calculating the sample size. 3. Subjects are not on any other treatment or any higher doses of metformin. They are asked to participate after the completion of a washout period of other previous medicines if any. 4. Assessment of glycemic control with HbA1C levels prior to intervention will not be done due to non-affordability of the patients to perform HBA1C test. 5. The term "diabetics" will be removed from the manuscript and will be replaced by "the patients suffering from Diabetes". 6. The dosage of Nishaamalaki is standardized by the dosage mentioned in classical texts of Ayurveda. Honey will not cause any rise in blood glucose level. A supporting mother article for this fact is available. Metformin and Nishamalaki, both are packaged and dosed in the same way. 7. Subjects who may withdraw the study will not be counted but will get replaced by other subjects until the calculated sample size gets completed. Therefore, it will not cause any bias. 8. Fasting and postprandial Blood glucose levels will be checked on day 0 and at day 60 as mentioned in the assessment criteria. 9. Secondary outcome will be properly formulated by mentioning the study of lowering BMI score. 10. Randomization through lottery method will be explained properly. 11. Result and discussion are just an expectation of the outcome, which will be completely based on the data received after the completion of study. 12. Other agents like food or spics that helps in the management of Diabetes Mellitus will be mentioned in the Introduction section instead of Discussion. 13. Conclusion will be formed only after receiving the data after completion of the study. Currently, it is merely an expectation. Respected Mam, Thanks for your valuable review and comments on my manuscript. I would like to respond on each comments given by you and do the necessary corrections in the study protocol as asked. I request you to kindly review the responses and corrections and give the approval if you find it appropriate as early as possible. 1. The mechanisms of T2 Diabetes mellitus will be explained in detail in the Introduction part. In paragraph 2 of the introduction part, by the end of this era means with the start of next generation. 2. The number of subjects are decided as per the appropriate statistical formula for calculating the sample size. 3. Subjects are not on any other treatment or any higher doses of metformin. They are asked to participate after the completion of a washout period of other previous medicines if any. 4. Assessment of glycemic control with HbA1C levels prior to intervention will not be done due to non-affordability of the patients to perform HBA1C test. 5. The term "diabetics" will be removed from the manuscript and will be replaced by "the patients suffering from Diabetes". 6. The dosage of Nishaamalaki is standardized by the dosage mentioned in classical texts of Ayurveda. Honey will not cause any rise in blood glucose level. A supporting mother article for this fact is available. Metformin and Nishamalaki, both are packaged and dosed in the same way. 7. Subjects who may withdraw the study will not be counted but will get replaced by other subjects until the calculated sample size gets completed. Therefore, it will not cause any bias. 8. Fasting and postprandial Blood glucose levels will be checked on day 0 and at day 60 as mentioned in the assessment criteria. 9. Secondary outcome will be properly formulated by mentioning the study of lowering BMI score. 10. Randomization through lottery method will be explained properly. 11. Result and discussion are just an expectation of the outcome, which will be completely based on the data received after the completion of study. 12. Other agents like food or spics that helps in the management of Diabetes Mellitus will be mentioned in the Introduction section instead of Discussion. 13. Conclusion will be formed only after receiving the data after completion of the study. Currently, it is merely an expectation. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 25 Sep 2023 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 4 5 Version 3 (revision) 04 Mar 24 read read Version 2 (revision) 24 Nov 23 read Version 1 25 Sep 23 read read read Naushira Pandya , Nova Southeastern University, Fort Lauderdale, USA Supriya Bhalerao , Bharati Vidyapeeth (Deemed to be) University, Pune, India Srihari Sheshagiri , JSS Ayurvedic Medical College, Mysore, India Yoshitaka Hashimoto , Matsushita Memorial Hospital, Moriguchi, Japan Raymond Tjandrawinata , Atma Jaya Catholic University of Indonesia, South Jakarta, Indonesia Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Tjandrawinata R. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 07 Jan 2025 | for Version 3 Raymond Tjandrawinata , Atma Jaya Catholic University of Indonesia, South Jakarta, Indonesia 0 Views copyright © 2025 Tjandrawinata R. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The protocol compares Nishaamalaki Churna with metformin for treating obese patients with type 2 diabetes mellitus (T2DM). The rationale is partly clear, as the study objective shifts focus between glycemic control and obesity without clearly differentiating the primary aim. The randomized design is appropriate, but blinding is problematic due to the differing forms of the drugs. Methodological details are insufficient, lacking clarity on sample size calculation, randomization, and adherence tracking. BMI is misclassified as an investigation instead of a study tool. Secondary outcomes could be expanded to better reflect obesity management. Ethical considerations and data-sharing plans need elaboration. Grammatical inconsistencies and premature conclusions predicting results need correction. Key Points for Scientific Soundness: Clarify the primary objective – whether the focus is glycemic control, obesity, or both. Address the limitations of blinding and correct BMI classification as a study tool. Provide comprehensive methodological details on sample size, randomization, and compliance monitoring. Expand secondary outcomes and specify ethical considerations and data-sharing practices. Addressing these issues will enhance the protocol’s clarity and reproducibility, improving its scientific rigor. Is the rationale for, and objectives of, the study clearly described? Partly Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? No Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests No competing interests were disclosed. Reviewer Expertise Pharmacology and Molecular Medicine I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Tjandrawinata R. Peer Review Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.163086.r353713) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1199/v3#referee-response-353713 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Hashimoto Y. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 10 Jun 2024 | for Version 3 Yoshitaka Hashimoto , Matsushita Memorial Hospital, Moriguchi, Japan 0 Views copyright © 2024 Hashimoto Y. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This protocol study will examine the effect of Nishaamalaki i n obese patients with type 2 diabetes mellitus. Several problems should be resolved. 1. Sample size. How to calculate the sample size was unclear. 2. Inclusion criteria were also unclear. The patients who were already used the medications for diabetes (without metformin) can participate? 3. BS-PP, FBS: These words should be spelled out. Furthermore, are FBS and BS-PP measured on the same day? How many minutes after a meal is BS-PP? Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? No Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests No competing interests were disclosed. Reviewer Expertise Diabetes, obesity I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Hashimoto Y. Peer Review Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.163086.r286660) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1199/v3#referee-response-286660 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Sheshagiri S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 08 Feb 2024 | for Version 2 Srihari Sheshagiri , Department of PG Studies in Kaumarabhritya, JSS Ayurvedic Medical College, Mysore, Karnataka, India 0 Views copyright © 2024 Sheshagiri S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions 1. Blinding may not be appropriate as two different forms of medicines are being administered. 2. Words used in the Randomisation paragraph (in methods section) are in past tense implying that the study is already concluded. The same needs proper grammatical correction. 3. What is the 'durable efficacy' in results needs to be defined 4. BMI is not an investigation rather an examination tool. The same can be removed from screening investigations, or the term tools can be used instead of investigation Competing Interests No competing interests were disclosed. Reviewer Expertise Ayurveda, Pediatrics I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 13 Apr 2024 Dr. Aman Chhabra, Kayachikitsa, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India Respected Sir Thanks for the comments given by you on my protocol. I would like to respond you with the rectifications in the comments. 1. The medicines in both the groups will be given separately to each patient with a proper randomisation. That's why the blinding is kept as appropriate even being two different forms of medicines. 2. The tense for the words used in Randimisation paragraph are now rectified. 3. Durable efficacy in results is now defined. 4. The term tools will be used instead of investigation as per your suggestion. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Sheshagiri S. Peer Review Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.159185.r225291) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1199/v2#referee-response-225291 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2023 Sheshagiri S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 21 Nov 2023 | for Version 1 Srihari Sheshagiri , Department of PG Studies in Kaumarabhritya, JSS Ayurvedic Medical College, Mysore, Karnataka, India 0 Views copyright © 2023 Sheshagiri S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Grammatical errors needs corrections, in few area present tense and in few area past tense has been utilised by the authors. In methods (abstract), inclusion of obese type 2 patients have been said a criteria for inclusion however in the article, BMI of 25-30 has been mentioned. One of the criteria to call a person obese is BMI above 30. Hence this needs clarity. Comparing the efficacy of trial drug and standard group has been mentioned as secondary outcome. However, the same a been mentioned as the main aim in abstract and in conclusion of the article. The same needs clarification. Is the rationale for, and objectives of, the study clearly described? Partly Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Partly Are the datasets clearly presented in a useable and accessible format? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Ayurveda, Pediatrics I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 30 Nov 2023 Dr. Aman Chhabra, Kayavhikitsa, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India Respected Sir, Thanks for your valuable review and comments on my manuscript. I would like to respond and clarify the comments given one by one. 1. Grammatical errors are now corrected and the entire manuscript is framed in future tense as per the guidelines for a protocol. 2. As per W.H.O., Obesity is a general term in which criteria of overweight has a classification of having B.M.I. score of 25-30 kg/m 2 , which is actually taken into consideration for this study protocol. , 3. The secondary outcome is now updated for better clarification. I request you to kindly review the corrected manuscript and if you feel satisfied with the corrections, kindly give your approval so as to proceed further in the peer review process. Looking forward for your kind response. Thanks View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Sheshagiri S. Peer Review Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.152287.r210017) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1199/v1#referee-response-210017 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2023 Bhalerao S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 21 Nov 2023 | for Version 1 Supriya Bhalerao , Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be) University, Pune, Maharashtra, India 0 Views copyright © 2023 Bhalerao S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The protocol is for assessing the efficacy of Nishamalaki in obesity, then why the introduction refers more to diabetes? ‘Type of trial’ is wrong term. It should be ‘study design’. How the blinding is possible? The nature of study drug and control drug is completely different-it should be an open study. There are no variables reflecting improvement in obesity e.g. body composition or circumferences, lipid profile. How the FBS and PPBS can give idea about anti-obesity efficacy? The authors need to decide whether they wish to demonstrate the efficacy of study drug in obesity or in diabetes. Is the rationale for, and objectives of, the study clearly described? No Is the study design appropriate for the research question? No Are sufficient details of the methods provided to allow replication by others? No Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests No competing interests were disclosed. Reviewer Expertise Obesity, Type 2 Diabetes, NAFLD, PCOS I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (1) Author Response 30 Nov 2023 Dr. Aman Chhabra, Kayavhikitsa, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India Respected Mam, Thanks for your valuable review and comments on my manuscript. I would like to respond and clarify the comments one by one. 1. As mentioned in the title, the study protocol is for assessing the efficacy of Nishaaamalaki and Metformin in obese patients suffering from Type-2 Diabetes Mellitus. The main focus is on Type-2 Diabetes Mellitus and not on obesity. Therefore, the Introduction refers more to Type-2 Diabetes Mellitus. 2. Type of trial is now replaced by Study design. 3. Blinding is for the allocation of groups not for the medicine. 4. Reduction in Body mass Index reflects improvement in obesity which is considered as the secondary outcome in this study. 5. It is totally clear and decided that the protocol is framed to compare the efficacy of trial and standard drug in obese patients suffering from Type-2 Diabetes Mellitus. I request you to kindly consider the responses and if you feel satisfied, then kindly give your necessary approval so that the peer review process can proceed further. Looking forward for your kind response. Thanks and Regards. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Bhalerao S. Peer Review Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.152287.r213873) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1199/v1#referee-response-213873 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2023 Pandya N. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 16 Nov 2023 | for Version 1 Naushira Pandya , Kiran Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, USA 0 Views copyright © 2023 Pandya N. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Comments: 1.The mechanisms for T2 diabetes could be expanded (eg; hepatic glucose production, renal reabsorption etc). What is meant by completion of this era in paragraph 2 of the Introduction? 2. How was the number of study subjects decided? 3. Are the subjects also on other treatments for diabetes, or even metformin at higher doses? 4. Will there be assessment of glycemic control in subjects prior to intervention with A1C levels? 5. The term "diabetics" is no longer used due to patients' objections. They are people with diabetes, and not defined by diabetes. 6. How is the dosage of Nishamalaki standardized? Will the honey cause a rise in blood glucose? If drugs are packaged in the same way, will metformin also be dosed the same way? 7. Will subjects who may withdraw still be counted in the final results (intention to treat)? Removing their data will bias the results. 8. How often will fasting and postprandial BG be checked? The Analytics section mentions day 15, 30, 45 but the Objectives state measurements at the start and day 60. 9. Secondary outcomes is poorly formulated. Subjects already have the disease, so disease recurrence does not seem valid and is repeated in the text. Monitoring for adverse effects is standard and is not a secondary outcome. Unless specific outcomes such as hospitalization, hypoglycemia, weight loss are being studied. 10. Randomization through lottery method needs to be explained further. If randomized, they cannot be assigned to a control or treatment group. 11. Since this is a methods paper, the Results section cannot possibly predict the results. The same applies to the Discussion section which mentions both metformin and Nishamalaki were effective in lowering blood glucose levels without any data to prove this. 12. Other agents in food or spices that are thought to lower blood glucose may be in the introduction to provide context, but NOT in the Discussion of the paper which is based on a specific research question. 13. Similarly the Conclusion section is premature without data or proof. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? No Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests No competing interests were disclosed. Reviewer Expertise Diabetes management in older adults I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 30 Nov 2023 Dr. Aman Chhabra, Kayavhikitsa, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India Respected Mam, Thanks for your valuable review and comments on my manuscript. I would like to respond on each comments given by you and do the necessary corrections in the study protocol as asked. I request you to kindly review the responses and corrections and give the approval if you find it appropriate as early as possible. 1. The mechanisms of T2 Diabetes mellitus will be explained in detail in the Introduction part. In paragraph 2 of the introduction part, by the end of this era means with the start of next generation. 2. The number of subjects are decided as per the appropriate statistical formula for calculating the sample size. 3. Subjects are not on any other treatment or any higher doses of metformin. They are asked to participate after the completion of a washout period of other previous medicines if any. 4. Assessment of glycemic control with HbA1C levels prior to intervention will not be done due to non-affordability of the patients to perform HBA1C test. 5. The term "diabetics" will be removed from the manuscript and will be replaced by "the patients suffering from Diabetes". 6. The dosage of Nishaamalaki is standardized by the dosage mentioned in classical texts of Ayurveda. Honey will not cause any rise in blood glucose level. A supporting mother article for this fact is available. Metformin and Nishamalaki, both are packaged and dosed in the same way. 7. Subjects who may withdraw the study will not be counted but will get replaced by other subjects until the calculated sample size gets completed. Therefore, it will not cause any bias. 8. Fasting and postprandial Blood glucose levels will be checked on day 0 and at day 60 as mentioned in the assessment criteria. 9. Secondary outcome will be properly formulated by mentioning the study of lowering BMI score. 10. Randomization through lottery method will be explained properly. 11. Result and discussion are just an expectation of the outcome, which will be completely based on the data received after the completion of study. 12. Other agents like food or spics that helps in the management of Diabetes Mellitus will be mentioned in the Introduction section instead of Discussion. 13. Conclusion will be formed only after receiving the data after completion of the study. Currently, it is merely an expectation. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Pandya N. Peer Review Report For: Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus ( Madhumeha ): A study protocol [version 3; peer review: 2 approved with reservations, 3 not approved] . F1000Research 2024, 12 :1199 ( https://doi.org/10.5256/f1000research.152287.r213867) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. 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